Study On Absorption Mechanism Of Lipophilic Components Of Danshen

Modern Chinese Medicine preparations are embodiments of modernity of Traditional Chinese Medicine (TCM). However, in order to modernize Chinese Medicine preparations, important things are to modernize pharmaceutical techniques, especially to modernize the theoretical basis of dosage forms selected and to modernize methods for screening prescriptions, optimizing technics and evaluating quality. Biopharmaceutics and Pharmacokinetics are subjects focusing on studying the regularities of drug's absorption, distribution, metabolism and elimination in vivo, and further elucidating the relationships between preparational factors, biological factors and drug effects. Thus, the purpose of this study is to provide novel ideas and approaches for selecting of dosage forms, screening of prescriptions, optimizing technics and evaluating quality by utilizing the latest measures and models of biopharmaceutics and pharmacokinetics.Complex prescription of Danqi is widely used to treat coronary disease. Lipophilic components of Danshen were used as model drugs. In the present study, mutiple-model including rat in situ perfusion preparation, Caco-2 monolayer model in vitro and kinetic research in vivo were employed systemically to investigate absorption mechanism of lipophilic components of dansehn and correlation among models, furthermore pharmaceutical measures were taken to promote bioavailability of lipophilic components orally administered. The results clearly indicated that lipophilic components of Danshen have low solubility and high permeability. The absorption mechanism of lipophilic components across the intestinal epithelium is rather complex andinvolves carrier-mediated transport and passive transcellular diffusion, without neither paracellular route nor P-gp efflux. Borneol can enhance absorption of lipophilic components. Ethanol extract of Danshen was subsequently administered to rats by intravenous or oral. The absolute bioavailabliy of tanshinone II a is rather low, as dissolving of lipophilic components limits the rate and extent of absorption of them across intestinal epithelium. Combination of ethanol extract of Danshen with borneol and cyclodextrin inclusion compound of Dansehn were administered to rats by oral, in which tanshinone II A has improved absolute bioavailability. Promoting solubility of lipophilic components of Danshen is a rather effective measure to improve their oral bioavailability. There exist rather qualitative than good quantitative correlation between Caco-2 monolayer model and rat in situ perfusion model, and good correlation between permeability in Caco-2 monolayer and fraction absorbed in vivo. We concluded that simple monolayer structure of a cultured cell system provides a distinct advantage in predicting in vivo drug absorption. In summary, we may achieve more reliable conclusion, by utilizing two or above methods to examine the seam drug and synthetically comparing and evaluating the results obtained form different methods.Due to there being no similar report, the accomplishment of the project is a great achieve of modernization of TCM as well as of biopharmaceutics and pharmacokinetics and provide a novel idea and method for researching and developing modern preparations of TCM with high effect, high quality and high standard.